Dexamethasone, Prednisolone, Fluorometholone, Loteprednol

Mechanism

💊 Commercial Names

Maxidex, Pred Forte, FML Forte, Lotemax, Tobradex (dexamethasone + tobramycin coformulation).

🔬 Pharmacological Group

Synthetic topical ophthalmic glucocorticoids. Loteprednol (a soft ester carbonate derivative).

🧪 Standard Formulations

Dexamethasone sodium phosphate 0.1%, prednisolone acetate 1.0% (suspension), fluorometholone alcohol 0.1%, loteprednol etabonate 0.5%.

Mechanism of Action

Topical corticosteroids cross the membrane of ocular inflammatory cells (macrophages, neutrophils, lymphocytes) by passive diffusion and bind to their specific cytoplasmic receptor (GR):

• Transactivation of Lipocortin-1 (Annexin-1): The activated glucocorticoid-receptor complex translocates to the cell nucleus and binds to glucocorticoid response elements (GREs). This increases the transcription of the Lipocortin-1, protein that directly inhibits the enzyme Phospholipase A₂ (PLA₂). When the PLA is blocked₂, the release of arachidonic acid from the phospholipids of the cellular membrane is prevented, stopping the synthesis of prostaglandins (COX pathway) and leukotrienes (LOX pathway) simultaneously.
• Transrepression of the Transcription Factor NF-κB: The activated GR complex blocks the cellular activity of NF-κB and AP-1, preventing the synthesis of inflammatory cytokines (IL-1, IL-2, IL-6, TNF-α), endothelial adhesion molecules (ICAM-1, VCAM-1) and local leukocyte chemotaxis.
• "Soft" or Site-Specific Corticosteroids (Loteprednol, Fluorometholone): Loteprednol etabonate is enzymatically metabolized in the eye ultra-rapidly to inactive metabolites derived from carboxylic acid after binding to GR. This reduces its penetration and persistence in the trabecular meshwork and the lens, sharply reducing the rate of adverse effects such as raised IOP and cataract formation compared to dexamethasone or prednisolone.

Pharmacokinetics

Quantitative Ocular and Systemic Pharmacokinetics

Glaucoma due to Corticosteroids and Cataracts: The Danger of Chronic Treatment

The uninterrupted use of powerful topical corticosteroids (especially dexamethasone and prednisolone) for more than 2 to 4 weeks can induce two serious ocular complications of silent course: 1) Corticonic (Steroridean) Glaucoma: Corticosteroids suppress the cellular enzymatic clearance in the trabecular meshwork of glycoproteins and polymeric glycosaminoglycans, and induce the myocilin protein expression. This promotes the accumulation of hydrophilic dural extracellular matrix that occludes the mesh, raising aqueous humor resistance and IOP in up to 30% of sensitive patients. 2) Posterior Subcapsular Cataracts: Alteration of sodium-potassium transport in the epithelial cells of the lens and collagen crystalline cells, inducing bilateral whitish opacities that are difficult to resolve non-surgically.

Security

Contraindications

• Absolute: Keratitis due to Herpes Simplex Virus of active epithelial type (typical dendritic lesions - corticosteroids suppress the local immune cellular response, promoting uncontrolled replication of the virus and causing a giant corneal geographic lesion with a necrotic course or corneal dural perforation); active ocular bacterial, fungal or mycobacterial infections not adequately treated with microbial coverage.
• Relative: Pre-existing primary open-angle glaucoma; unstable diabetes.

Adverse Effects (ADR)

• Local Ocular: Elevation of IOP (steroid-induced ocular hypertension, dose-dependent); formation of posterior subcapsular cataracts; significant delay in corneal epithelial healing (inhibition of collagen synthesis and keratocyte mitosis); scleral perforation in eyes with pathological thinning (due to metalloproteinase induction); transient eyelid ptosis; mild pupillary mydriasis.
• Systemic: Rare with topical ocular use at correct doses. In low weight children or with extremely frequent doses, it can induce suppression of the hypothalamic-pituitary-adrenal axis of exogenous origin.

Drug Interactions

• Anti-VEGF or Antiglaucomatous Agents: Topical corticosteroids can moderately attenuate some peripheral cellular repair effects of these agents or annul their ocular hypotensive efficacy by direct trabecular elevation.